Anterior medial temporal lobe activation during encoding of words: FMRI methods to optimize sensitivity

The existence of a rostrocaudal gradient of medial temporal lobe (MTL) activation during memory encoding has historically received support from positron emission tomography studies, but less so from functional MRI (FMRI) studies. More recently, FMRI studies have demonstrated that characteristics of the stimuli can affect the location of activation seen in the MTL when those stimuli are encoded. The current study tested the hypothesis that MTL activation during memory encoding is related to the modality of stimulus presentation. Subjects encoded auditorily or visually presented words in an FMRI novelty paradigm. Imaging and analysis parameters were optimized to minimize susceptibility artifact in the anterior MTL. Greater activation was observed in the anterior than posterior MTL for both modalities of stimulus presentation. The results indicate that anterior MTL activation occurred during encoding, independent of stimulus modality and provide support for the hypothesis that verbal-semantic memory processing occurs in anterior MTL. The authors suggest that technical factors are critical for observing the rostrocaudal gradient in MTL memory activation.     

Cholinergic modulation of the hippocampus during encoding and retrieval of tone/shock-induced fear conditioning

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with no effect on tone conditioning. Cholinergic antagonists also impair acquisition of contextual conditioning. Saline, scopolamine, or physostigmine was administered directly into the CA3 subregion of the hippocampus 10 min before rats were trained on a tone/shock-induced fear conditioning paradigm. Freezing behavior was used as the measure of learning. The scopolamine group froze significantly less during acquisition to the context relative to controls. The scopolamine group also froze less to the context test administered 24 h posttraining. A finer analysis of the data revealed that scopolamine disrupted encoding but not retrieval. The physostigmine group initially froze less during acquisition to the context, although this was not significantly different from controls. During the context test, the physostigmine group froze less initially but quickly matched the freezing levels of controls. A finer analysis of the data indicated that physostigmine disrupted retrieval but not encoding. These results suggest that increased ACh levels are necessary for encoding new spatial contexts, whereas decreased ACh levels are necessary for retrieving previously learned spatial contexts.     

Verbal cues facilitate memory retrieval during infancy

In three experiments, 18-month-olds were tested in a deferred imitation paradigm. Some infants received verbal information during the demonstration and at the time of the test (full narration), and some did not (empty narration). When tested after a 4-week delay, infants given full narration exhibited superior retention relative to infants given empty narration (Experiment 1). This retention advantage appears to be due to the effects of verbal cues at the time of memory retrieval. There was no effect of verbal cues that were presented only at the time of original encoding (Experiment 2A). Furthermore, infants who received verbal cues only at the time of retrieval exhibited superior retention relative to infants who received verbal cues only at the time of original encoding (Experiment 2B). These findings demonstrate that verbal cues can enhance memory retrieval by participants who are not yet fluent speakers themselves.     

The hippocampus and prefrontal cortex are differentially involved in serial memory retrieval in non-stress and stress conditions

We previously showed that 24 h after learning, mice significantly remembered the first (D1) but not the second (D2) discrimination in a serial spatial task and that an acute stress delivered 5 min before the test phase reversed this memory retrieval pattern.A first experiment evaluated the effects of dorsal hippocampus (HPC) or prefrontal cortex (PFC) lesions, these two brain areas being well-known for their involvement in serial and spatial memory processes. For this purpose, six independent groups of mice were used: non-lesioned (controls), PFC or HPC-lesioned animals, submitted or not to an acute stress (electric footshocks; 0.9 mA). Results show that (i) non-stressed controls as well as PFC-lesioned mice (stressed or not) remembered D1 but not D2; (ii) stressed controls and HPC-lesioned mice (stressed or not) remembered D2 but not D1; (iii) stress significantly increased plasma corticosterone in controls and PFC-lesioned mice, but not in HPC-lesioned mice which already showed a significant plasma corticosterone increase in non-stressed condition.Since data from this first experiment showed that stress inhibited the hippocampal-dependent D1 memory retrieval, a second experiment evaluated the behavioral effect of intrahippocampal corticosterone injection in non-stressed mice. Results show that intrahippocampal corticosterone injection induced a reversal of serial memory retrieval pattern similar to that induced by acute stress.Overall, our study shows that (i) in non-stress condition, the emergence of D1 is HPC-dependent; (ii) in stress condition, the emergence of D2 requires the PFC integrity; moreover, intrahippocampal corticosterone injection mimicked the effects of stress in the CSD task.     

Acetylcholine modulation of neural systems involved in learning and memory

Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation. This paper reviews evidence for cholinergic regulation of multiple memory systems, noting that manipulations of cholinergic functions in many neural systems can enhance or impair memory for tasks generally associated with those neural systems. While parallel memory systems can be identified by combining lesions with carefully crafted tasks, most—if not all—tasks require the combinatorial participation of multiple neural systems. This paper offers the hypothesis that the magnitude of acetylcholine (ACh) release in different neural systems may regulate the relative contributions of these systems to learning. Recent studies of ACh release, obtained with in vivo microdialysis samples during training, together with direct injections of cholinergic drugs into different neural systems, provide evidence that release of ACh is important in engaging these systems during learning, and that the extent to which the systems are engaged is associated with individual differences in learning and memory.     

The roles of encoding strategies and retrieval practice in test-expectancy effects

We investigated whether expectations for different kinds of memory tests induce qualitatively different encoding strategies. In Experiment 1, participants studied four lists of words and after each list completed a cued-recall test that contained either all semantic or all orthographic cues so as to build up an expectancy for receiving the same type of test for the fifth critical study list. To rule out that the test-expectancy effects in Experiment 1 were due to differences in retrieval practice, in Experiment 2, participants received three practice tests each for both cue-types. Participants’ test expectancy for all lists was induced by telling them before each list the type of cue they would receive for the upcoming study list. In both experiments, the critical test contained both expected and unexpected cues. In Experiment 1, participants who expected semantic cues had better recall to the semantic cues than to the orthographic cues and vice versa for those who expected orthographic cues. However, in Experiment 2, there was no effect of test expectancy. These findings suggest that the test-expectancy effects in Experiment 1 were due to more retrieval practice on the expected than unexpected tests rather than to qualitatively different test-expectancy-induced encoding strategies.     

Cholinergic modulation of learning and memory in the human brain as detected with functional neuroimaging

The advent of neuroimaging methods such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has provided investigators with a tool to study neuronal processes involved in cognitive functions in humans. Recent years have seen an increasing amount of studies which mapped higher cognitive functions to specific brain regions. These studies have had a great impact on our understanding of neuroanatomical correlates of learning and memory in the living human brain. Recently, advances were made to go beyond the use of fMRI as a pure cognitive brain mapping device. One of these advances includes the use of psychopharmacological approaches in conjunction with neuroimaging. The paper will introduce the combination of neuroimaging and psychopharmacology as a tool to study neurochemical modulation of human brain function. A review of imaging studies using cholinergic challenges in the context of explicit and implicit learning and memory paradigms is provided which show that cholinergic neurotransmission modulates task-related activity in sensory and frontal cortical brain areas.     

The effect of encoding time on retention by infants and young children

Using a Visual Recognition Memory (VRM) procedure, we examined the effect of encoding time on retention by 1- and 4-year olds. Irrespective of age, shorter familiarization time reduced retention, and longer familiarization time prolonged retention. The amount of familiarization that yielded retention after a given delay decreased as a function of age.     

提取练习效应的产生机制:编码、提取的整合演变

提取练习效应指相比同等时间的重复学习,对所学材料进行提取练习(即使无反馈)可使被试在之后的回忆测验中表现更好。早期研究从编码或提取单维度地对提取练习效应进行了描述性解释,新近以来,研究者整合了编码和提取在提取练习效应中的作用,从记忆加工全过程的角度考察了提取练习效应的产生机制,并得到诸多研究证据的支持。论文梳理了提取练习效应产生机制的各类假说,并重点分析比较了精细提取假说和情景背景假说,指出后者在解释提取练习效应上的优势。未来研究可结合认知神经科学的研究技术为情景背景假说提供更直接的证据,有关提取练习对于短期和长期记忆促进效果的争议也有待进一步解释厘清,同时如何在揭示其原理的基础上将其更高效地加以应用亦有待实践探索。     

Effect of unpleasant loud noise on hippocampal activities during picture encoding: an fMRI study

The functional link between the amygdala and hippocampus in humans has not been well documented. We examined the effect of unpleasant loud noise on hippocampal and amygdaloid activities during picture encoding by means of fMRI, and on the correct response in humans. The noise reduced activity in the hippocampus during picture encoding, decreased the correct response and increased the activity of the amygdala. A path diagram using structural equation modeling suggested that hippocampus activity might be depressed by high amygdala activity. Therefore, noise should diminish memory by reducing hippocampal activity, which might be depressed by high amygdala activity.     

Coordination of multiple memory systems

On the basis of lesions of different brain areas, several neural systems appear to be important for processing information regarding different types of learning and memory. This paper examines the development of pharmacological and neurochemical approaches to multiple memory systems from past studies of modulation of memory formation. The findings suggest that peripheral neuroendocrine mechanisms that regulate memory processing may target their actions toward those neural systems most engaged in the processing of learning and memory. In addition, measurements of acetylcholine release in different memory systems reveals extensive interactions between memory systems, some cooperative and some competitive. These results imply that many neural systems, often characterized as relatively independent, may in fact interact extensively, blurring the dependencies of different memory tasks on specific neural systems.     

记忆编码中目标与背景的情绪一致性对记忆提取的影响

摘 要 本研究将经典情绪启动范式和学习-再认范式相结合,探讨学习时启动与目标的情绪一致性对目标再认的影响。在记忆编码阶段,以情绪面孔图片为启动刺激、一般情绪图片为目标刺激,要求被试对目标图片的效价进行判断;在提取阶段向被试呈现一般情绪图片,要求被试判断是否在前一阶段见过。结果表明,编码阶段的加工背景对记忆提取产生了显著影响。一致启动促进了认知加工与记忆编码,提高了再认正确率。ERP结果也表明,在目标刺激呈现后300-500ms,编码时的情绪一致性对再认阶段消极目标诱发的ERP产生了显著影响。     

The role of semantically related distractors during encoding and retrieval of words in long-term memory

We examined the influence of divided attention (DA) on recognition of words when the concurrent task was semantically related or unrelated to the to-be-recognised target words. Participants were asked to either study or retrieve a target list of semantically related words while simultaneously making semantic decisions (i.e., size judgements) to another set of related or unrelated words heard concurrently. We manipulated semantic relatedness of distractor to target words, and whether DA occurred during the encoding or retrieval phase of memory. Recognition accuracy was significantly diminished relative to full attention, following DA conditions at encoding, regardless of relatedness of distractors to study words. However, response times (RTs) were slower with related compared to unrelated distractors. Similarly, under DA at retrieval, recognition RTs were slower when distractors were semantically related than unrelated to target words. Unlike the effect from DA at encoding, recognition accuracy was worse under DA at retrieval when the distractors were related compared to unrelated to the target words. Results suggest that availability of general attentional resources is critical for successful encoding, whereas successful retrieval is particularly reliant on access to a semantic code, making it sensitive to related distractors under DA conditions.     

Age-related changes in frequency of mind-wandering and task-related interferences during memory encoding and their impact on retrieval

During the performance of cognitive tasks such as memory encoding, attention can become decoupled from the external environment and instead focused on internal thoughts related to the appraisal of the current task (task-related interferences; TRI), or personal thoughts unrelated to the task at hand (mind-wandering; MW). However, the association between the frequency of these thoughts experienced at encoding and retrieval accuracy in young and older adults remains poorly understood. In this study young and older adults encoded lists of words using one of two encoding tasks: judging whether words are man-made/natural (objective task), or whether they are pleasant/neutral (subjective task). We measured the frequency of TRI and MW at encoding, and related them to retrieval accuracy in both age groups. We found that encoding task influenced the type of internal thoughts experienced by young, but not older, adults: young exhibited greater MW in the subjective vs the objective task, and greater TRI in the objective vs subjective encoding task. Second, across both tasks we found marked age-related decreases in both MW and TRI at encoding, and frequency of these thoughts negatively impacted memory retrieval in young adults only. We discuss these findings in relation to current theories of ageing, attention and memory.     

Spatial learning induces differential changes in calcium/calmodulin-stimulated (ACI) and calcium-insensitive (ACII) adenylyl cyclases in the mouse hippocampus

Several lines of evidence indicate that Ca2+/calmodulin-stimulated isoforms of adenylyl cyclase (AC) are involved in long-term potentiation and in certain forms of learning. Recently, we found that training in different types of learning task differentially activates Ca2+-sensitive versus Ca2+-insensitive AC activities in certain brain regions, indicating that AC species other than those stimulated by Ca2+/calmodulin may play an important role in learning processes (Guillou, Rose, & Cooper, 1999). Here, we report the effects of spatial reference memory training in a radial arm maze on the levels of AC1 and AC2 mRNA in the dorsal hippocampus of C57BL/6 mice. Acquisition of the task was associated with a learning-specific and time-dependent increase of AC1 mRNA expression selectively in subfields CA1-CA2. In contrast, AC2 mRNA levels were either reduced or not reliably affected depending on the stage of acquisition. Moreover, no significant changes in AC expression were observed either in the dorsal hippocampus of mice trained in a non-spatial (procedural) version of the task or in cortical regions of mice learning the spatial or procedural task. The regional specificity of these effects indicates that the formation of spatial and non-spatial memory requires distinct contributions from Ca2+-sensitive and Ca2+-insensitive AC in the hippocampus. It is suggested that downregulation of AC2 throughout all hippocampal subfields may play a permissive role during the acquisition of spatial learning whereas an upregulation of AC1 specifically in subfield CA1, may be critical to accurately encode, store or use spatial information.     

Memory for emotional words: The role of semantic relatedness,encoding task and affective valence

Emotional stimuli have been repeatedly demonstrated to be better remembered than neutral ones. The aim of the present study was to test whether this advantage in memory is mainly produced by the affective content of the stimuli or it can be rather accounted for by factors such as semantic relatedness or type of encoding task. The valence of the stimuli (positive, negative and neutral words that could be either semantically related or unrelated) as well as the type of encoding task (focused on either familiarity or emotionality) was manipulated. The results revealed an advantage in memory for emotional words (either positive or negative) regardless of semantic relatedness. Importantly, this advantage was modulated by the encoding task, as it was reliable only in the task which focused on emotionality. These findings suggest that congruity with the dimension attended at encoding might contribute to the superiority in memory for emotional words, thus offering us a more complex picture of the underlying mechanisms behind the advantage for emotional information in memory.     

An integrated model of eye movements and visual encoding

Recent computational models of cognition have made good progress in accounting for the visual processes needed to encode external stimuli. However, these models typically incorporate simplified models of visual processing that assume a constant encoding time for all visual objects and do not distinguish between eye movements and shifts of attention. This paper presents a domain-independent computational model, EMMA, that provides a more rigorous account of eye movements and visual encoding and their interaction with a cognitive processor. The visual-encoding component of the model describes the effects of frequency and foveal eccentricity when encoding visual objects as internal representations. The eye-movement component describes the temporal and spatial characteristics of eye movements as they arise from shifts of visual attention. When integrated with a cognitive model, EMMA generates quantitative predictions concerning when and where the eyes move, thus serving to relate higher-level cognitive processes and attention shifts with lower-level eye-movement behavior. The paper evaluates EMMA in three illustrative domains — equation solving, reading, and visual search — and demonstrates how the model accounts for aspects of behavior that simpler models of cognitive and visual processing fail to explain.     

Hippocampus, cortex, and basal ganglia: insights from computational models of complementary learning systems

We present a framework for understanding how the hippocampus, neocortex, and basal ganglia work together to support cognitive and behavioral function in the mammalian brain. This framework is based on computational tradeoffs that arise in neural network models, where achieving one type of learning function requires very different parameters from those necessary to achieve another form of learning. For example, we dissociate the hippocampus from cortex with respect to general levels of activity, learning rate, and level of overlap between activation patterns. Similarly, the frontal cortex and associated basal ganglia system have important neural specializations not required of the posterior cortex system. Taken together, this overall cognitive architecture, which has been implemented in functioning computational models, provides a rich and often subtle means of explaining a wide range of behavioral and cognitive neuroscience data. Here, we summarize recent results in the domains of recognition memory, contextual fear conditioning, effects of basal ganglia lesions on stimulus-response and place learning, and flexible responding.     

In Praise of a Model but Not Its Conclusions: Commentary on Cooper,Catmur, and Heyes (2012)

Cooper et al. (this issue) develop an interactive activation model of spatial and imitative compatibilities that simulates the key results from Catmur and Heyes (2011) and thus conclude that both compatibilities are mediated by the same processes since their single model can predict all the results. Although the model is impressive, the conclusions are premature because they are based on an incomplete review of the relevant literature and because the model includes some questionable assumptions. Moreover, a competing model (Scheutz & Bertenthal, 2012) is introduced that suggests the two compatibilities are not mediated by the same processes. We propose that more research is necessary before concluding that spatial and imitative compatibilities are mediated by the same processes.     

Temporary inactivation of dorsal hippocampus attenuates explicitly nonspatial, unimodal, contextual fear conditioning

The current study examined the effects of temporary inactivation of the DH on freezing, rearing, ambulating, grooming, and whisking behavior in an explicitly nonspatial contextual fear conditioning paradigm in which olfactory stimuli served as temporally and spatially diffuse contexts. Prior either to training, testing, or both, male Sprague–Dawley rats received bilateral microinfusions of saline or the GABA_A agonist muscimol into the DH. Results indicate that temporary inactivation of DH produced both anterograde and retrograde deficits in contextually conditioned freezing, while sparing the acquisition and expression of freezing to a discrete auditory or olfactory CS. These data suggest that there is a decidedly nonspatial component to the role of DH in contextual conditioning, and that olfactory contextual conditioning is a fruitful means of further exploring this function.